Biomedical subjects

Layne T Watson

Publications and source records attributed to Layne T Watson.

5 recordsLinked to original sources

PubMed2005

Parameter estimation for a mathematical model of the cell cycle in frog eggs.

Parameter values for a kinetic model of the nuclear replication-division cycle in frog eggs are estimated by fitting solutions of the kinetic equations (nonlinear ordinary differential equations) to a suite of experimental observations. A set of optimal parameter values is found by minimizing an objective function defined as the orthogonal distance between the data and the model. The differential equations are solved by LSODAR and the objective function is minimized by ODRPACK. The optimal parameter values are close to the "guesstimates" of the modelers who first studied this problem. These tools are sufficiently general to attack more complicated problems, where guesstimation is impractical or unreliable.

Animals↗

PubMed2004

the JigCell model builder and run manager.

SUMMARY: We describe the JigCell Model Builder (JCMB), a tool for creating biochemical reaction network models. JCMB is designed for ease of use and its interface uses the standard spreadsheet metaphor. The JigCell Run Manager (JCRM) is a tool for organizing the large collections of simulation runs typically required by reaction network modeling activities. AVAILABILITY: JCMB and JCRM are part of the JigCell suite available at http://jigcell.biol.vt.edu.

Animals↗

PubMed2003

Modeling regulatory networks at Virginia Tech.

The life of a cell is governed by the physicochemical properties of a complex network of interacting macromolecules (primarily genes and proteins). Hence, a full scientific understanding of and rational engineering approach to cell physiology require accurate mathematical models of the spatial and temporal dynamics of these macromolecular assemblies, especially the networks involved in integrating signals and regulating cellular responses. The Virginia Tech Consortium is involved in three specific goals of DARPA's computational biology program (Bio-COMP): to create effective software tools for modeling gene-protein-metabolite networks, to employ these tools in creating a new generation of realistic models, and to test and refine these models by well-conceived experimental studies. The special emphasis of this group is to understand the mechanisms of cell cycle control in eukaryotes (yeast cells and frog eggs). The software tools developed at Virginia Tech are designed to meet general requirements of modeling regulatory networks and are collected in a problem-solving environment called JigCell.

Animals↗

PubMed2003

Photosynthetic acclimation is reflected in specific patterns of gene expression in drought-stressed loblolly pine.

Because the product of a single gene can influence many aspects of plant growth and development, it is necessary to understand how gene products act in concert and upon each other to effect adaptive changes to stressful conditions. We conducted experiments to improve our understanding of the responses of loblolly pine (Pinus taeda) to drought stress. Water was withheld from rooted plantlets of to a measured water potential of -1 MPa for mild stress and -1.5 MPa for severe stress. Net photosynthesis was measured for each level of stress. RNA was isolated from needles and used in hybridizations against a microarray consisting of 2173 cDNA clones from five pine expressed sequence tag libraries. Gene expression was estimated using a two-stage mixed linear model. Subsequently, data mining via inductive logic programming identified rules (relationships) among gene expression, treatments, and functional categories. Changes in RNA transcript profiles of loblolly pine due to drought stress were correlated with physiological data reflecting photosynthetic acclimation to mild stress or photosynthetic failure during severe stress. Analysis of transcript profiles indicated that there are distinct patterns of expression related to the two levels of stress. Genes encoding heat shock proteins, late embryogenic-abundant proteins, enzymes from the aromatic acid and flavonoid biosynthetic pathways, and from carbon metabolism showed distinctive responses associated with acclimation. Five genes shown to have different transcript levels in response to either mild or severe stress were chosen for further analysis using real-time polymerase chain reaction. The real-time polymerase chain reaction results were in good agreement with those obtained on microarrays.

Acclimatization↗

PubMedDate not supplied

The JigCell model builder: a spreadsheet interface for creating biochemical reaction network models.

Converting a biochemical reaction network to a set of kinetic rate equations is tedious and error prone. We describe known interface paradigms for inputing models of intracellular regulatory networks: graphical layout (diagrams), wizards, scripting languages, and direct entry of chemical equations. We present the JigCell Model Builder, which allows users to define models as a set of reaction equations using a spreadsheet (an example of direct entry of equations) and outputs model definitions in the Systems Biology Markup Language, Level 2. We present the results of two usability studies. The spreadsheet paradigm demonstrated its effectiveness in reducing the number of errors made by modelers when compared to hand conversion of a wiring diagram to differential equations. A comparison of representatives of the four interface paradigms for a simple model of the cell cycle was conducted which measured time, mouse clicks, and keystrokes to enter the model, and the number of screens needed to view the contents of the model. All four paradigms had similar data entry times. The spreadsheet and scripting language approaches require significantly fewer screens to view the models than do the wizard or graphical layout approaches.

Algorithms↗